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TRAF2 is an NF-?B-activating oncogene in epithelial cancers.

ABSTRACT: Aberrant nuclear factor (NF)-?B activation is frequently observed in human cancers. Genome characterization efforts have identified genetic alterations in multiple components of the NF-?B pathway, some of which have been shown to be essential for cancer initiation and tumor maintenance. Here, using patient tumors and cancer cell lines, we identify the NF-?B regulator, TRAF2 (tumor necrosis factor (TNF) receptor-associated factor 2), as an oncogene that is recurrently amplified and rearranged in 15% of human epithelial cancers. Suppression of TRAF2 in cancer cells harboring TRAF2 copy number gain inhibits proliferation, NF-?B activation, anchorage-independent growth and tumorigenesis. Cancer cells that are dependent on TRAF2 also require NF-?B for survival. The phosphorylation of TRAF2 at serine 11 is essential for the survival of cancer cells harboring TRAF2 amplification. Together, these observations identify TRAF2 as a frequently amplified oncogene.

SUBMITTER: Shen RR

PROVIDER: S-EPMC4067463 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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TRAF2 is an NF-κB-activating oncogene in epithelial cancers.

Shen R R RR Zhou A Y AY Kim E E O'Connell J T JT Hagerstrand D D Beroukhim R R Hahn W C WC

Oncogene 20131223 2

Aberrant nuclear factor (NF)-κB activation is frequently observed in human cancers. Genome characterization efforts have identified genetic alterations in multiple components of the NF-κB pathway, some of which have been shown to be essential for cancer initiation and tumor maintenance. Here, using patient tumors and cancer cell lines, we identify the NF-κB regulator, TRAF2 (tumor necrosis factor (TNF) receptor-associated factor 2), as an oncogene that is recurrently amplified and rearranged in ...[more]

PMID: 24362534

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